Compounds of quinin and dialkylbarbituric acids.



unit dielh l url ituric acid :1 stuted in ex UNITED STATES PATENT OFFICE.

CLAUS UIEHL, 0F DARMSTALUT, GERMANY, ASSIGNOR TO E. MERCK, (2F DARMSTADT, GERMANY A COPARTNERSHIIP.

Specification of Letters Patent.

No Drawing.

Patented June 6, 1916.

Application filed September 18, 1912. Serial No. 720,176.

T11 all whom only mmcern:

lie it known that l, Dix Fidel/T 1 1215111,, u, ubjccim" the K and a :resi dent oi humm- Efdu (he iiriin fi Duchy of Hesse. ll i'nmu limping hufo invented ceri'uiu new and zssclui luxpi'owinenis in oanpounds of Quinin :ind Dinlliylburbiturio lipids of lliil'li the lolhming is it specificatioiz.

My imcn oo relates lu'omliy lo new and useful compounds m" umin with lllillli'yl" bui-biiurii acids, and methmls of producing the same end more specifically to com-)inw lions oi uuiniii with diethylburbituric acid :inil the homologous (lifllliffl mlllllllllc acids, for inslunce. dipriipylhurliituric acid.

I have diseoiei-ed, utter painstaking experimcms tlnit contrary to i'uevious experiments und knowledge, it is possible to prmlme will crystallized and shui'ply deliu u-l (he in \i voi-upmunls oi uuinin and the din? H acids. :Ulfl that the thorn politic action oi the hen class of bodies in no um represents simply the sum of the no is till, intensified action, and one which is modified, in a favorable manner.

The invention also contemplates combinations of salts of quinin with diulkylbarbiturio acids in producing the new product.

The new combinations are obtained through the interaction of the molecular quantities of the free compounds, or their salts, effectively in the presence of proper solvents.

I will now give certain examples of proce- (lure my means of which the new substances or compounds may be produced.

Example 1 I take 65 grams of quinin and proportional quantity of dialkylbarbituric acid, in this instance 37 gr. diethylbzn-bituric acid being used, and boil the two wmponents together for some time in approximately 400 c. c. of chloroform. I have found that when the ingredients are in the above proportion, and the proportional amount of solvent used is as stated, that boiling for half an hour will cause the desired reaction to take place. This reactions oi lioth components out; illSlIfiHl there lion I believe to be as follows.

on. ,co-oziu C185 ,co nn )og oo+omuuuiop c oo qownnmoo only -i,-o-nn mu, co-un hituriite may be separated in any suiti'o'le mannen Example 3: Aqueous solutions of a salt of quinin, for instance, of 19.8 grams of quinin hydrochloritl, and a salt of dialk lbarbituric acid for instance of 10.3 grams s0- ofium diethylbai'biturzite, are combined and the mixture is boiled for a considerabletime say for two hours. The precipitate which is se uii'uted on mixing the two components gradually into solution and after cooling quinin diethylbnrbituric acid crystallizes out as drusy crystalline conglomeration. The reaction which takes place in this example is as follows.

By the boiling the vlilmnform is evaporated :1 udo upon slhll evupm'otioin u residue is produced solidified in the form of crystals, us l|llllllll-(liltll \il):lllllilH'iC ucid. The yield is quunlitzitivellxumple 1: The same quantities of quinin umplc i time in nmli'culur proportion are melted ton'etlu" im- :1 short time. say for a hull" hour l Hm zwllino the quinindiv fylli-irbitm'ii' :uiil i-- produced. The re suiting! g lusw pl'mllu't it the reaction thi-n l'lli'l lll up will alcohol, ether or me time. 'lhei'ehv it is trumlonued into the colorless crystalline muss l'ioin which the new compound, that is, qiiiuin-diethyllmr- The new compound has the characteristics of being formed in clear crystals anclbeing easily soluble in hot alcohol, ChlOEOfOIm, acetone and ethylucetate, u l ttle less soluble in hot water, other and cold benzol, and

The proportions given in this third example are for the salt referred to therein and, of course, may vary with other salts of quinin and (llltllyliiill'llltlll'llf acid or diolkylburbituric acids which may be employed.

2 mosaic? diflicultly soluble in cold water, or ligroin, and almost insoluble in petroleum ether. The new substance, quinindiethylbarbituric acid, according to thc abovc cxainplcs of procedure, crystallizes out as a drusy couglomeration of acidular crystals. lts melting point is 13 (I It winsists ot' om anoic cnlc each of quinin and dicthylbarliituric acid, the formula of thc compound prmluccd by the aboi'c cxamplcs being probably, and I believe it to bc As above stated in placc of dicthylbarbituric acid, I may also cinploy othcr dialkyh barbituric acids; that is, the homologous (lialkylbarbarituric acids, such as dipropylbarbituric acid, the nlcthod of proccdurc in the production of the new substance bcing the same, or substantially thc sanic, as set forth in the abovc examples.

All of the con'ipounds of quinin with dialkylbarbit-uric acids are easily split up, by treatment with dilute hydrochloric acid to form a quinin salt, 2'. 0., quinin hydro-- chlorid, and frcc dialkylbarbituric acid. lVhen treated with an alkali. i'or instancc, soda lye, thc said compounds arc (locomposed into frcc quinin and the alkali salt of dialkylbarbituric acid, the lattcr whcn soda lye is used, being sodium dialliylharl)ituratc. These decomposition reactions arc ClHU'tlCt0l'- istic for all compounds of dialliylbarbituric acids with quinin.

Applying the above tests to the coimumn-il of dicthyllmrbituric acid with quiniu, the compound when trcatcdwith dilutc hydro i-hloric acid would split up into quinin hydrochlorid and free diethylbarbituric acid, and upon treatment with soda lye, thc t'rcc quinin base and sodium dicthylbarbiturate are formed.

In certain of the accompanying claims, I employ the expression a quinin compound in a gcneric sense to include both the t'rcc basc quinin and also its salts. Similarly the expressions a compound comprising a dialkylbarbituric acid radical and a compound comprising a diethylbarbituric acid radical are cmployed gcncrically to include the lrcc acids specified and their salts.

\Vhat I claim and desire to secure by Letters Patent is:

1. As a now article of manufacture, a concpound of quiuin, and a dialkylbarbituric acid and having the probable formula 3 c0 Gammon and which upon treatment with dilute hydrochloric acid splits up into quinin hydrochlorid and frcc tiallqylbarbituric acid.

2; As a new article of manufacture, a

combination of quinin and diethylbarbit-uric acid having the probable formula C I ico c nn mon m u uand which upon triaitmcnt with dilute hydrochloric acid sg'ilits up into quinin hydrochlorid and l'rcc d'cihylbarbituric acid.

The nicthod at producing coi'npounds of quinin and a di; lh'yllJilIbltllllC acid which consists in causing' a quinin compound and a compoinu'l comprising a diallcylbarbituric acid radical to react in the prcscncc of so]- v nts- The i cthod of producing compounds of ouiizin and a diallrvlbarbituric acid which consists in causing a ouiuin compound and a wunpound comprising a dialliylbarbituric acil radical to react undnr tho influence of boat,

I). The method of producing compounds of quinin and a dialkylbarbituric acid which consists in causing a quinin compound and a compound con'iprising a dialkylbarbituric acid radical to react in the presence of solvents and under the influence of heat.

Tho mcthod of producing compounds of r uinin and a dialkylbarbituric acid which in causing aqueous solutions of a quinin compound and a compound comprising: a dialkylbarbituric acid radical to react under the im'luencc of hcat.

7. The method of producing compounds of quinin and a diallqylbarbituric acid which consists in heating a quinin compound and a compound comprising a dialkylbarbituric acid radical in a solycnt until the same react, and evaporating; the solvent until thc residuc solidilics in crystalline form.

8. The method 01 producin compounds of iguiuin and a diallcylbarhituric acid which consists in boiling a salt of quinin and a salt ot a dialkylbarhituric acid in a solvent until the same rcact and separating the quinim diallrylharbituratc after cooling.

5). The method of producing quinindi-"tliylbarbiturate which consists in boiling to wilt)! a quinin compound and a diethylbarhituric acid compound until they react and separating the quinin-diethylbarbiturate by cooling.

i0. The method of producing quinindiothyll'mrbiturate which consists in boiling together a salt of quinin and a salt of dicthylbarhituric acid in a suitable solvent until the same react and separating the quininalicthylbarbiturate after cooling.

11. As a new article of manufacture, a well defined crystalline compound of quinin and a dialkylbarbituric acid, resulting from the combination of quinin and a dialkylbarbituric acid in molecular proportions, said compound upon treatment with dilute hydrochloric acid splitting up into quinin acid.

hydrochlor'id and free dialkylbarbituric In testimony whereoi I have hereunto 13 signed my name in the presence of two sub- 12. As a. new article of manufacture, a scribing witnesses.

well defined c stalline compound of quinin' and diethylb r ituric acid in molecular pro- CLAUS DIEHL.

nrtions, sgad compound upon treatment Witnesses: ith dilute! hydrochloric acid splitting up JEAN GRUND,

into qminin h drochlorigi and free diethyl- CARL GRUND.

barbiturie' aci 

